Thursday, March 29, 2012

When I first heard of the endowed chair position created at the University of Wisconsin by Glaxo Wellcome to support the work of the University of Wisconsin's Center for Tobacco Research and Intervention, I assumed that the funding was intended to support a broad range of loosely defined research in the general area of tobacco control, consistent with the overall mission of the Center for Tobacco Research and Intervention.

John Polito, however, has brought it to my attention that the memorandum of agreement which established the endowed chair position defines a narrow range of supported activities that all focus on nationally marketing smoking cessation drugs. The four activities are specified as follows:

Each of these areas relates to the development or marketing of smoking cessation drugs:

1. Disseminating the AHCPR guidelines appears intended to make sure that all clinicians are aware that every smoking patient should be treated with pharmacotherapy.

2. Encouraging insurance companies to cover smoking cessation drugs appears intended to increase the use of these smoking cessation drugs by removing financial barriers to their use.

3. The development of innovative pharmacotherapies is of course directly related to the development of new or improved smoking cessation drugs.

4. Expanding public education about the availability of pharmacotherapy is of course intended to increase the national use of these drugs.

The Rest of the Story

Essentially, what Glaxo Wellcome has brilliantly done here is to establish what you might call a national marketing office disguised as an objective research center. Through this generous gift, the Center and its Chair are essentially made partners with Glaxo Wellcome in the effort to market smoking cessation drugs nationally by increasing awareness of specific guidelines that physicians must use these drugs to treat every smoking patient, trying to remove financial barriers to the use of these drugs, and educating the public about the option of pharmaceuticals to encourage them to increase their use of these drugs.

In other words, Glaxo effectively established a national "research" center for the encouragement of all smokers to use smoking cessation drugs and for the encouragement of all physicians to prescribe smoking cessation drugs to all their smoking patients.

It is striking to me how narrow the language is in this memorandum. Usually, I think of endowed chairs as non-specific documents which provide broad, general support for the work of a professor, certainly specifying a general area of research interest, but usually not proscribing an exact course of action and specific set of allowable activities under the research program.

For example, if Dr. Fiore became interested in cold turkey quitting, this memorandum does not appear broad enough to allow him to pursue research in the use of cold turkey quitting as a smoking cessation strategy. More importantly, it removes any incentive from he or others in the Center from doing so because it is clearly not in the financial interest of the sponsor.

Given the clear conflict created by the creation of this endowed position by a pharmaceutical company and the clearly narrow scope of allowable activities which all are focused on the marketing of smoking cessation drugs, it would appear to have been especially important to ensure that the endowed chair not have any other (that is, personal) financial conflicts of interest with pharmaceutical companies that manufacture smoking cessation drugs. The funding itself is one thing, but if the chair also had personal conflicts of interest with Big Pharma, such as consultancies, these would seem inappropriate under this new arrangement.

Unfortunately, it appears that Dr. Fiore, during at least the approximate years 1999 through 2005, did receive consulting income and honoraria from pharmaceutical companies and was therefore a conflicted investigator holding a Big Pharma-endowed chair.

To be clear, there is nothing wrong with the idea of educating the public or physicians about the availability of smoking cessation drugs and about recommendations for the use of these drugs. Glaxo was not asking the Center to do anything inappropriate. However, if that is going to be your mission, it is important to do so objectively. And that requires a non-conflicted investigator in the chair position.

In my view, there is nothing a priori wrong with a university accepting an endowed professorship from a pharmaceutical company. However, two things are essential.

First, the holder of that chair should be a non-conflicted individual.

Second, the scope of the work must be broadly defined, rather than defined specifically as activities which are tantamount to the national marketing of that company's products or potential products. Otherwise, the university must be willing to call a spade a spade and admit that the funded institution is basically serving as a marketing arm of the pharmaceutical company, helping it to do its bidding. This may not be a bad thing because the drugs do help some people quit smoking, but we need to be honest about what is going on.

There is harm, however, when this type of situation is handled wrongly and a conflicted investigator is put in the endowed chair position, funded by Big Pharma. while at the same time, the allowable activities are narrowly drawn to ensure a focus on the marketing of pharmaceutical products. What happens is that you now have a conflicted individual running a marketing program funded by a pharmaceutical company. The research activities now lose their scientific objectivity.

The harm comes when as a result of the exclusive focus on these smoking cessation drugs, the Center loses a broader perspective and fails to disseminate important research about the failings of smoking cessation drugs, their serious risks, and the research showing that cold turkey quitting is actually more effective than planned attempts with NRT.

I find it quite revealing, for example, that in the news archives of the UW-CTRI, I cannot find a single article about the dangers of Chantix. There is an article from 2009 highlighting a study which found no suicide increase due to Chantix, although it couldn't rule out a two-fold increase in suicide due to small sample size. But why no link to this 2011 article linking Chantix and suicide, or to this 2011 article reporting that there have been 272 suicides associated with Chantix, or to this 2010 study in the Annals of Pharmacology?

Buying an endowed chairmanship under these conditions buys you more than simply the opportunity to say that you've made a philanthropic contribution. In the case of the endowed chair at UW-CTRI, it gives you an opportunity to essentially control the agenda, the emphasis, and the presentation of the scientific information about pharmaceutical products to the public. Big Pharma has certainly got its money's worth.

Tuesday, March 27, 2012

As I discussed here last week, in an article published in the New England Journal of Medicine, Dr. Michael Fiore and colleagues defend the new Joint Commission tobacco cessation performance measure set for hospitals, which - strikingly - insists that every smoking patient be discharged with a prescription for a smoking cessation drug (unless it is specifically contraindicated or the patient refuses).

Today, I explain why this policy is misguided and how unfortunately it is that the policy results from an expert panel chair with multiple financial conflicts of interest with Big Pharma.

The Rest of the Story

Physician autonomy is one of the most important factors that I believe is essential to ensure the quality and integrity of medical care. When autonomy to treat patients in the best interest of the patient is taken away from physicians for any reason, whether it be economic or political, it erodes the quality of medical care, undermines the physician-patient relationship, and threatens to undo the essential element of medical practice upon which the entire practice relies.

This is precisely what has happened with the Joint Commission standard for the treatment of smoking cessation among hospitalized patients. Rather than allow each physician to treat his patient in the way he see fits, the Commission policy requires the physician to treat his patient by prescribing, at discharge, a smoking cessation drug.

I can think of no other area of medical practice where physician autonomy has been so completely taken away by the Joint Commission. If a patient is admitted with hypertension, the physician can treat the patient in any way she sees fit. That may involve an anti-hypertensive drug, but it may also involve weight loss and diet modification. In many cases, diet modification and weight loss are sufficient to control blood pressure, and a drug prescription may not be required. Can you imagine if the Joint Commission required every doctor to prescribe an anti-hypertensive medication at discharge? That would destroy physician autonomy, although it would be a boon for the pharmaceutical companies that make anti-hypertensive drugs.

If a patient is admitted with type II diabetes, the physician can make a judgment about what treatment plan is best for that particular individual. For some, a glucose-controlling drug will be required. For others, weight loss alone may be enough to solve the problem. It is up to the physician to take the particular patient into account and make the decision that is in the best interest of her patient. No one in an unbiased frame of mind would require the physician to prescribe a drug when there are other possible modes of treatment that could be effective.

If a patient is admitted with depression, it is up to the physician to decide whether an anti-depression drug is appropriate, or whether psychotherapy or other treatment modalities are most appropriate for that particular patient. Not so with the Joint Commission's treatment of smoking cessation. Unlike all of the above examples, drug treatment is mandated, regardless of whether the physician believes it is in the best interest of the patient.

That physician autonomy is being undermined would be bad enough. But what makes the situation truly unacceptable is that an apparent reason for this undermining of physician autonomy is the presence of a highly conflicted chair of the advisory panel that helped formulate the smoking cessation treatment criteria. The chair of that panel has a long history of financial conflicts of interest with Big Pharma, especially with companies that manufacture the very drugs that the Joint Commission recommendation is requiring physicians to prescribe.

What a financial windfall for the pharmaceutical companies. They must be laughing all the way to the bank, wondering how lucky they could possibly be that despite the long-standing principle of physician autonomy, somehow the Joint Commission has decided to force doctors to prescribe their drugs to just about every smoking patient. I doubt that even the pharmaceutical companies ever thought they would get that lucky.

The rest of the story is that every dollar that the pharmaceutical companies pay to tobacco researchers for consulting, grants, or honoraria is money well spent. It comes back to the companies in spades, more than offsetting the initial expenditures. This is perhaps the grandest example of the dangers of financial conflicts of interest. In this case, the conflict of interest has not only created a boon for pharmaceutical companies, but it has done nearly the unthinkable: produce an official medical treatment recommendation that disrespects physician autonomy, requiring physicians to prescribe a drug regardless of whether they believe that particular treatment modality is in the best interest of their patient.

The study was conducted in a real-world, population-based setting, using the national quitline in England to recruit participants. Callers to the quitline who agreed to set a quit date were randomized to one of the following groups:

The participants were randomized in a 2 by 2 design. Thus, one group was usual care only. One group was intervention A only. One group was intervention B only. And the fourth group received Intervention A and Intervention B.

The findings were as follows: The six-month prolonged cessation rate for those who received free NRT was 17.7%, compared to a rate of 20.1% among those who did not receive free NRT. This difference was not statistically significant.

For validated smoking cessation at six months (confirmed by carbon monoxide testing), the quit rates were 6.6% for those who received free NRT and 9.4% for those who did not receive free NRT. This difference was statistically significant.

Depending on whether one relies upon the confirmed or unconfirmed smoking cessation results, the basic finding of the study is either that NRT had no effect on quitting, or that the provision of free NRT slightly impaired smoking cessation.

The study concludes: "Among smokers who were motivated enough to call the English NHS Smoking Helpline, set a quit date, and accepted an offer of support for smoking cessation, offering either additional free nicotine replacement therapy or higher intensity proactive telephone support did not increase quit rates over and above those obtained using standard quitline care."

The Rest of the Story

The most important finding of this story is that under the best real-life conditions of free nicotine replacement therapy and frequent counseling, a chemically-confirmed six-month smoking cessation rate of only 6.6% was achieved. Even the non-confirmed (self-reported) quit rate of 17.7% at six months among those who received free NRT is quite dismal.

Compare these findings with those of the first electronic cigarette trial. In that study, the sustained six-month abstinence rate was 22.5%.

There was a major difference, however. In this study, the smokers were highly motivated to quit and had gone so far as to call the quitline. In the Polosa study, subjects were enrolled only if they had "no interest in quitting."

Thus, we have a real-world six-month prolonged cessation rate of 17.7% with NRT among highly motivated smokers compared to a 22.5% prolonged six-month cessation rate with electronic cigarettes among smokers with very low motivation to quit.

Do anti-smoking practitioners look at the evidence anymore? In light of these data, what would possibly prompt anti-smoking groups to highly encourage NRT, highly discourage electronic cigarettes, and even go so far as to advise electronic cigarette users who have successfully quit to return to "proven" methods of cessation?

Moreover, what is the difference between this research and the previous research which purportedly showed how effective NRT is?

I assert that there are two major differences:

1. The previous research was not conducted in a real-life setting. It was conducted in the settings of clinical trials which in no way simulate people's actual experience outside of those trials. Here, the research involved a clinical trial, but it was conducted in a real-life, population-based setting which represents actual practice.

2. The previous research was conducted largely by researchers with financial conflicts of interest with Big Pharma. This research was conducted by investigators with no financial conflicts of interest.

As the evidence continues to build that NRT is not all that it was cracked up to be, the established tobacco control institutions are not budging because they are too financially entrenched in Big Pharma. As I have pointed out in just the last week, their conferences are sponsored by Big Pharma, their organizations are heavily funded by Big Pharma, and their major reports and recommendations giving national advice or setting national policy are written largely by experts who have financial conflicts of interest with Big Pharma.

About Me

Dr. Siegel is a Professor in the Department of Community Health Sciences, Boston University School of Public Health. He has 32 years of experience in the field of tobacco control. He previously spent two years working at the Office on Smoking and Health at CDC, where he conducted research on secondhand smoke and cigarette advertising. He has published nearly 70 papers related to tobacco. He testified in the landmark Engle lawsuit against the tobacco companies, which resulted in an unprecedented $145 billion verdict against the industry. He teaches social and behavioral sciences, mass communication and public health, and public health advocacy in the Masters of Public Health program.